Research Abstracts We propose to develop and evaluate optimal combinations of evidence-based interventions (EBIs) to improve HIV outcomes and reduce methamphetamine use among people with opioid use disorder (OUD) who are in methadone maintenance therapy (MMT) in Vietnam (STAR-OM study). Over the past decade, the expansion of MMT has contributed to stemming both HIV and opioid epidemics. However, rising methamphetamine use threatens these achievements. The twinned epidemics of opioid and methamphetamine use have also been reported in the US and other countries. Building on our pilot work with MMT patients in Hanoi, through collaborative work with local MMT providers and patients, we will refine adapted EBIs to develop an adaptive design that offers an individualized approach to treatment. The adaptive design includes: (1) Two frontline interventions: 6 weeks of CM then 6 weeks of weekly group educational sessions (low intensity CM) and 12 weeks of CM (high intensity CM); (2) One (short-term) tailoring outcome: urine tests negative with meth metabolites in both week 11 and 12 are considered responsive to frontline interventions; (3) Three alternative interventions: those with positive outcomes will move to 12-week maintenance stage and receive two daily SMS reminders plus one weekly self-monitoring assessment message. Non-responders will move to 12-week enhanced treatment stage and are randomized to either Matrix group counseling only or Matrix group counseling plus CM. We will compare effectiveness of two frontline interventions and four adaptive interventions with a Sequential Multiple Assignment Randomization Trial in 200 HIV+ (150 from HCMC; 50 from Hanoi) and 400 HIV- (200 from each city) MMT patients who report moderate- and high-risk meth use on self-screening with tablet-based ASSIST and/or have urine positive with methamphetamine metabolites. In each location, the study will stratify participants by HIV status before randomizing them to one of two frontline interventions. Primary outcomes - including HIV viral suppression, HIV risk behaviors, and meth use (reported and urine tests) - will be assessed at 12, 24 and 48 weeks. We will calculate the incremental cost effectiveness ratio (ICER) comparing cost-effectiveness between two frontline interventions as well as among four adaptive strategies. Finally yet importantly, we also conduct ethnographic observations and in-depth interviews with MMT clinic managers, clinical staff and MMT patients (N=60, 30 per city) to identify structural, provider and patient-level factors that influence adoption and scale-up of the adaptive interventions. Findings from this study with Type I Hybrid design to evaluate EFFECTIVENESS-Implementation will provide valuable evidence to develop treatments in resourced and resourced-constrained settings to confront the twinned epidemics of opioid and methamphetamine use in the context of surging HIV epidemic due to drug abuse.